Hirata and Axelrod have recently described two phospholipid methyltransferases that convert phosphatidylethanolamine to phosphatidylcholine by three successive N-methylations and transport the phospholipid from the inner to the outer monolayer of a cell membrane. The action is stimulated by beta-adrenergic agonists and other ligands for membrane receptors and is reported to cause a substantial reduction in the viscosity of the membrane. Hirata and Axelrod believe that the disordering directly facilitates a number of pharmacological events such as stimulation of adenylate cyclase, release of histamine, etc. The decreased microviscosity on incubation with the methyl donor has been demonstrated only in erythrocytes; its magnitude is surprisingly large. This is a most exciting finding if it can be confirmed. I propose to attempt to reproduce this finding, since I have several years' experience with measurement of membrane fluidity in response to drugs. Specifically, I plan to test the hypothesis that large changes in membrane fluidity accompany the phospholipid transformations. In preliminary spin label experiements I have found no change in membrane stiffness of mouse synaptosomal plasma membranes under conditions where the enzymes are active. I now plan to repeat the Hirata and Axelrod experiment with red cell ghosts, using fluorescence anisotropy of diphenylhexatriene to estimate the viscosity of the membrane, as they did. I will also repeat my preliminary experiments with spin-labeled brain membranes, using reagents of greater purity and more appropriate conditions for the EPR determinations.